A miRNA-Based Blood and Mucosal Approach for Detecting and Monitoring Celiac Disease

Dig Dis Sci. 2020 Jul;65(7):1982-1991. doi: 10.1007/s10620-019-05966-z. Epub 2019 Nov 28.

Abstract

Background: The role of microRNAs (miRNAs) in celiac disease (CD) is unclear.

Aims: We evaluated inflammation-related miRNA-146a, miRNA-155, miRNA-21, and miRNA-125b expression in peripheral blood and intestinal mucosa of CD adults.

Methods: Thirty patients with CD were included: patients with active CD on a gluten-containing diet (CD-active, n = 10), patients on a gluten-free diet (for at least 1 year), and patients with negative blood antibodies (CD-inactivePE, n = 10). In addition, ten healthy volunteers formed the comparison/control group. MiRNA expression was measured in duodenal biopsies from patients (CD-inactiveMU, n = 10) after in vitro exposure to PT gliadin and 33-mer peptide. MiRNAs expression was measured in plasma and in peripheral blood mononuclear cells (PBMCs) and monocytes, before and after in vitro exposure to native gliadin (gliadinN).

Results: Expression levels of miRNA-146a, miRNA-155, and miRNA-21 in PBMCs, miRNA-155 in monocytes and miRNA-155, miRNA-21, and miRNA-125b in plasma were elevated in both groups of celiac patients. After in vitro exposure with gliadinN, miRNA-146a and miRNA-155 expression markedly increased in PBMCs and monocytes, while miRNA-155 and miRNA-21 increased in the CD-active group. MiRNAs expression in intestinal mucosa did not change. MiRNA-146a and miRNA-155 expression showed high sensitivity and specificity for the presence of CD, irrespective of the current dietary treatment.

Conclusions: Selected inflammation-related miRNAs expression is elevated in the peripheral blood of celiac. This suggests their participation in the immune processes underlying the pathology. Their similar response in active and inactive CD suggests that they should be further evaluated, as potential diagnostic biomarkers for CD.

Keywords: Celiac disease; Gliadin; Inflammation; MicroRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Celiac Disease / blood
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Celiac Disease / metabolism*
  • Diet, Gluten-Free
  • Female
  • GTP-Binding Proteins / immunology
  • HLA-DQ Antigens / genetics
  • Humans
  • Immunoglobulin A / immunology
  • Intestinal Mucosa / metabolism*
  • Male
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • Middle Aged
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology

Substances

  • HLA-DQ Antigens
  • Immunoglobulin A
  • MIRN125 microRNA, human
  • MIRN146 microRNA, human
  • MIRN155 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins